It is now widely accepted that tumor growth is dependent on angiogenesis. Many preliminary results from our laboratory and others suggest that normal tissue is similarly dependent on the vascular endothelium for growth. To study the role of angiogenesis in the growth of normal tissue, the mechanisms by which organs growth is regulated will be explored. Regenerating and non-regenerating implanted spleen fragments in mice will be used as a model to assess the role of angiogenesis in the regulation of total spleen mass. The effects of angiogenic stimulation or inhibition on spleen regeneration will be determined and a comparison of the angiogenic phenotype and gene expression in regenerating and non-regenerating spleen fragments will be made. These studies will lend insight into the molecular mechanisms of spleen regeneration control, will expand our understanding of angiogenesis in general, and will provide much information about the role of angiogenesis in the regulation of normal tissue growth.